PROJECT SUMMARY Despite being a preventable and treatable disease, tuberculosis (TB) kills just under 2 million people annually, and vulnerable populations, especially people living with HIV (PLWH), are at highest risk for disease and death. In Brazil, TB rates are markedly higher in PLWH and preventing TB for PLWH is a top priority. However, our prior work in Rio de Janeiro estimated only 12% of eligible PLWH receiving TB preventive therapy annually and identified two critical constraints to delivery of effective TB preventive therapy among PLWH: tuberculin skin testing (TST) for latent TB infection (LTBI) and adherence to 6 months of isoniazid preventive therapy (IPT). With QFT+, a 4th generation Interferon Gamma Release Assay, LTBI status can be determined as part of routine blood draws without the patient having to return to the clinic. This strategy has the potential to substantially improve the TB/HIV prevention continuum. PREVINE-TB (PRevent: EValuating the Implementation of NEw strategies for preventing TB among people living with HIV in Brazil) will test use of QFT+ and compare adherence strategies to optimize implementation of the TB prevention continuum in HIV clinics in Brazil. A switch from daily isoniazid to the novel 3HP regimen (once weekly for 12 weeks), now recommended by the CDC, may improve patient adherence, but may also be a challenge in not being part of a daily routine. The 3HP regimen was recently added to guidelines for PLWH as an alternative to the 6-month course of IPT in Brazil, but the best method for implementing 3HP is yet to be determined. PREVINE-TB has the potential to increase uptake for this at-risk population in a setting where PLWH have been shown (by our team) to significantly benefit from preventive therapy. Our goal is to assess the implementation by the Brazilian National Tuberculosis Program (NTP) of a novel strategy to prevent TB among PLWH in Brazil. Aim 1 will focus on QFT+ as a strategy to increase screening for LTBI as part of routine care for PLWH. We will determine the effectiveness and costs of QFT+ linked to routine viral load and CD4 blood draws to optimize the TB/HIV prevention care continuum. Aim 2 will determine effectiveness and cost-effectiveness of three scalable methods for optimizing patient adherence to 3HP. We will conduct an individually randomized non-inferiority trial of adherence for PLWH eligible for 3HP to compare clinic-based directly observed therapy (DOT, the current standard-of-care) vs self-administered therapy (SAT) with optimized text messaging. Finally, we will utilize (Aim 3) the Consolidated Framework for Implementation Research (CFIR) to optimize intervention processes and describe key elements for the successful implementation of the QFT+ and 3HP strategies to inform scale-up and maintenance. Using a mixed methods approach, we will explore perspectives from three stakeholder groups (patients, providers, and program managers/policy makers) to build and improve optimal intervention implementation. This evaluation will help ensure study results are directly translated into policy in the most appropriate and cost-effective manner.